In vitro antimicrobial activity of aztreonam alone and in combination against bacterial isolates from pediatric patients

Abstract

We examined 134 pediatric clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and grampositive cocci for susceptibility to aztreonam alone and in combination with seven other antibiotics. All

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

“…Similar to in vitro synergy evaluations against P. aeruginosa, earlier analyses of Enterobacteriaceae primarily consisted of beta-lactams no longer available or infrequently used. Consistent with the P. aeruginosa in vitro studies, synergy was commonly observed with dual beta-lactam combination regimens that included aztreonam (Buesing and Jorgensen, 1984;Sader et al, 2003;Stutman et al, 1984) or a third-generation cephalosporin (Buesing and Jorgensen, 1984;Daschner and Hoffmann, 1982;Tsuchiya, 1981a, 1981b;Kurtz et al, 1981;Miles et al, 1981;Neu, 1982;Sader et al, 2003;Verbist and Verhaegen, 1984;Zinner et al, 1981). Combinations including mecillinam were also found to be highly successful against Enterobacteriaceae in earlier analyses, where synergistic interactions were observed against a high proportion of all pathogens (Anderson et al, 1981;Baltimore et al, 1976;Chattopadhyay and Hall, 1979;Cleeland and Squires, 1983;Fass, 1980Fass, , 1982aFass, , 1982bTsuchiya, 1981a, 1981b;Schaad et al, 1982;Scheld et al, 1979;Tybring and Melchior, 1975;van der Voet et al, 1983).…”

“…Similar to the P. aeruginosa studies, beta-lactam combinations consisting of cefoxitin were commonly antagonistic against Enterobacteriaceae (Fass, 1980;Kuck et al, 1981;Markowitz and Sibilla, 1983;Stutman et al, 1984). Moxalactam and first-generation cephalosporins, such as cefazolin and cephalothin, were also found to be antagonistic when combined with other beta-lactams (Buesing and Jorgensen, 1984;Fass, 1982aFass, , 1982bFu and Neu, 1978;Kuck et al, 1981;Neu and Fu, 1978;Verbist and Verhaegen, 1984).…”

“…Most of these studies used broth or agar dilution or the checkerboard method to test for synergy (Anderson et al, 1981;Baltimore et al, 1976;Bosso et al, 1990;Bosso et al, 1991;Buesing and Jorgensen, 1984;Chattopadhyay and Hall, 1979;Chen et al, 2004;Cleeland and Squires, 1983;Daschner and Hoffmann, 1982;Drusano et al, 1985;Fass, 1980;Fass, 1982aFass, , 1982bFoweraker et al, 2009;Fu and Neu, 1978;Tsuchiya, 1981a, 1981b;Kuck et al, 1981;Kurtz et al, 1981;Markowitz and Sibilla, 1983;Miles et al, 1981;Moody et al, 1984;Neu, 1982;Neu and Fu, 1978;Peterson et al, 1984;Sader et al, 2003;Schaad et al, 1982;Scheld et al, 1979;Scribner et al, 1982;Song et al, 2003;Stutman et al, 1984;Tybring and Melchior, 1975;van der Voet et al, 1983;Verbist and Verhaegen, 1984;Wu et al, 1984;Zinner et al, 1981), but time-kill studies were also done (Foweraker et al, 2009;Fu and Neu, 1978;Tsuchiya, 1981a, 1981b;Lister et al, 1998;Markowitz and Sibilla, 1983;…”

Evaluation of aztreonam in the treatment of severe bacterial infections

“…High levels of AZT in serum can be obtained with a 1-g parenteral dose, protein binding is about 56%, and the terminal half life in serum is 1.7 h. AZT is not metabolized in the body, renal excretion occurs by glomerular filtration, and about 65% of the antibiotic is recovered unchanged from the urine (18,29,(31)(32)(33).…”

“…The compound is inactive against aerobic, gram-positive and anaerobic bacteria. It is likely that this selective spectrum of action causes minimal disturbance of normal human fecal flora, thus decreasing the risk of overgrowth of enterococci and other resistant strains (12,15,21,23,34,35).High levels of AZT in serum can be obtained with a 1-g parenteral dose, protein binding is about 56%, and the terminal half life in serum is 1.7 h. AZT is not metabolized in the body, renal excretion occurs by glomerular filtration, and about 65% of the antibiotic is recovered unchanged from the urine (18,29,(31)(32)(33).With these considerations in mind, we evaluated the clinical efficiency, tolerance, and toxicity of AZT in the treatment of 46 patients with 50 episodes of severe bacterial infections. …”